PB2426: SORAFENIB MAINTENANCE TAILORED TO FLT3-MUTATED AML AFTER ALLOGENEIC HCT IS HIGHLY FEASIBLE AND EFFECTIVE: A REAL-LIFE EXPERIENCE
Authors: Elisa Diral, Giulia Furnari, Francesca Farina, Daniela Clerici, Sarah Marktel, Raffaella Greco, Gloria Catalano, Alessandro Bruno, Edoardo Campodonico, Elisabetta Xue, Sara Mastaglio, Luca Vago, Massimo Stefano Luca Bernardi, Matteo Giovanni Carrabba, Consuelo Corti, Jacopo Peccatori, Fabio Ciceri, Maria Teresa Lupo Stanghellini
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Acute myeloid leukemia (AML) with mutation of the FMS-like tyrosine kinase 3 gene (FLT3) remains to this day one of the greatest challenges of modern haematology, due to poor prognosis despite allogeneic hematopoietic stem cell transplantation (HCT). FLT3 inhibitors - such as the multi-targeted tyrosine kinase inhibitor sorafenib - have proved their efficacy in both induction and salvage treatment. The use of sorafenib in maintenance after HCT is part of the ALWP (acute leukemia working party) - EBMT (European Society for Blood and Marrow Transplantation) recommendation to optimize long-term disease control. Of note, the use of FLT3-inhibitors in maintenance after HCT is off-label, although sorafenib proved to be safe and efficient in significantly reducing cumulative incidence of relapse and improving survival. Aims: The aim of our study is to evaluate the safety and efficacy in preventing early and late relapse in AML-FLT3+ after HCT. Methods: We hereby report data from 20 adult patients with FLT3-ITD+ AML receiving sorafenib after HCT between Feb-2017 and Feb-2023 (patients features are reported in table 1). Sorafenib was given off-label after provision of an informed signed consent. Fourteen patients in complete remission (CR) after HCT received sorafenib as a maintenance treatment for high-risk disease; 5 patients received sorafenib due to molecular relapse, while 1 patient was given sorafenib as a salvage therapy for hematologic relapse after HCT. Of note, 14 patients received FLT3 inhibitors prior to transplant (in association with first line chemotherapy or as salvage therapy). Results: The median time of initiation of sorafenib from HCT was 118 days (49-904). The median follow-up is 1414 days (180-2252) and the median treatment duration was 698 days (3-1431). Nine patients are currently under treatment - median treatment duration 405 days (80-1382). Sorafenib was introduced at minimum dosage of 200 mg daily, to reduce the drug-drug-interaction with concomitant therapies. Six patients required a reduction to 200 mg every-other-day to mitigate the gastro-intestinal discomfort. One patient was able to increment the dosage up to the maximum dosage of 400 mg twice daily without toxicities as well. Sorafenib was overall well-tolerated, with only 2 patients discontinuing it for grade 3 – CTC AE toxicity (one gastro-intestinal toxicity and one cardiac toxicity). Two patients discontinued sorafenib due to disease progression (1 patient after 860 days, and was rescued with a second HCT; 1 patient after 200 days, and died from overt relapse). Eight patients completed the 2-years maintenance with sorafenib – median time of treatment 965 days (651 - 1431). All but one maintained a persistent long-lasting response – median follow-up from discontinuation 634 days (480 - 1280). A single patient restarted sorafenib due to early re-appearance of MRD+ in two subsequent controls: after resumption of sorafenib, MRD negativity was achieved soon after and he is still in CR. Overall, 16/18 patients with FLT3-ITD+ AML achieved stable long-lasting CR, with none of them experiencing major long-term toxicity. Summary/Conclusion: Our real-life practice confirms that sorafenib maintenance therapy is well-tolerated and contributes to sustained long-lasting remissions of FLT3+ AML after allogeneic HCT. Sorafenib should be considered a feasible and effective therapeutic option as maintenance drug in this post-transplant context.Keywords: flt3 inhibitor, Allogeneic hematopoietic stem cell transplant, Acute myeloid leukemia, FLT3